Erdman - Penicillins Flashcards
Beta-lactam general characteristics
-Inhibit cell wall synthesis
-Bacteria resistances include beta-lactamase degradation, PBP alteration, decreased penetration
-Bactericidal in a time-dependent manner, except against enteroccocus
-Short elimination half-life
-Primarily excreted unchanged by the kidneys
-Cross-allergenicity in class
Beta-lactams that are not eliminated by the kidneys
-Nafcillin
-Oxacillin
-Ceftriaxone
-Cefoperazone
Beta-lactam that does not have cross-allergenicity
Aztreonam
Which gram-positive bacteria produce beta-lactamase enzymes?
Penicillin-resistant Staphylococcus aureus
Which gram-negative bacteria produce beta-lactamase enzymes?
-Haemophilus influenza
-Moraxella catarrhalis
-Neisseria gonorrhoeae
-E. Coli
-Klebsiella pneumoniae
-Enterobacter spp.
-etc.
Which gram-negative anaerobes produce beta-lactamase enzymes?
Bacterioides fragilis
Which bacteria alter the structure of PBPs leading to decreased binding affinity?
-Methicillin-resistant Staphylococcus aureus (MRSA)
-Penicillin-resistant Streptococcus pneumoniae (PRSP)
Three mechanisms of bacterial resistance against antibiotics
-Production of beta-lactamase enzymes
-Alterations in the structure of PBPs leading to decreased binding affinity
-Alterations of outer membrane porin proteins leading to decreased penetration
What are the natural penicillins used clinically?
-Aqueous penicillin G
-Benzathine penicillin G
-Procaine penicillin G
-Phenoxymethyl penicillin (penicillin VK)
Penicillin spectrum of activity against gram-positives
-Group streptococci
-Viridans streptococci
-Enterococcus spp.
-Pen-susceptible S. pneumoniae
-Pen-susceptible S. aureus
-Bacillus spp.
Penicillin spectrum of activity against gram-negatives
-Primarily used against some cocci
-Neisseria spp.
-Pasteurella multocida
Penicillin spectrum of activity against anaerobes
-Above the diaphragm
-Clostridium spp. but not C. diff.
Most important bacteria that penicillin covers
Treponema pallidum (syphilis)
Why were penicillinase-resistant penicillins developed?
In response to the emergence of penicillinase-producing Staph aureus
Examples of penicillinase-resistant penicillins
-Nafcillin
-Methicillin (no longer used)
-Dicloxacillin
Which penicillinase-resistant penicillin is oral?
Dicloxacillin
Penicillinase-resistant penicillin spectrum of activity against gram-positives
-Group streptococci
-Viridans streptococci
-Methicillin-susceptible S. aureus (MSSA)* (DOC)
Penicillinase-resistant penicillin spectrum of activity against gram-negatives
No activity against gram-negatives
Penicillinase-resistant penicillin spectrum of activity against anaerobes
No activity
What are the aminopenicillins?
-Ampicillin
-Amoxicillin
Which aminopenicillins are oral?
-Ampicillin
-Amoxicillin
Which aminopenicillins are parenteral?
Ampicillin
Aminopenicillin spectrum of activity against gram-positives
-Group streptococci
-Viridans streptococci
-Pen-susc S. pneumoniae
-Enterococcus spp. (DOC)*
-Pen-susc S. aureus
Aminopenicillin spectrum of activity against gram-negatives
(SHEP)
-Salmonella, shigella
-H. influenzae (beta-lactamase negative)
-E. coli (some)
-Proteus mirabilis
What are the carboxypenicillins?
Ticarcillin (parenteral)
Carboxypenicillin spectrum of activity against gram-positives
None
Carboxypenicillin spectrum of activity against gram-negatives
(SHEPEP)
-Salmonella, shigella
-H. influenzae (beta-lactamase positive)
-E. coli (some)
-Proteus mirabilis
-Enterobacter spp.
-Pseudomonas aeruginosa*
What are the ureidopenicillins?
Piperacillin
Is piperacillin parenteral or oral?
Parenteral
Ureidopenicillin spectrum of activity against gram-positives
-Group strep
-Viridans strep
-Some enterococcus (Amp is still doc)
Ureidopenicillin spectrum of activity against gram-negatives
(SHEPEP + KS)
-Salmonella, shigella
-H. influenzae (beta-lactamase positive)
-E. coli (some)
-Proteus mirabilis
-Enterobacter spp.
-Pseudomonas aeruginosa* (DOC)
-Some klebsiella spp.
-Serratia marcescens
What are the beta-lactamase inhibitor combo products?
-Ampicillin-sulbactam (Unasyn)
-Piperacillin-tazobactam (Zosyn)
-Amoxicillin-clavulanate (Augmentin)
What is Unasyn?
Ampicillin-sulbactam
What is Zosyn?
Piperacillin-tazobactam
What is Augmentin?
Amoxicillin-clavulanate
Ureidopenicillin spectrum of activity against anaerobes
-Fairly good activity
-BDA
-Mostly used in combo with beta-lactamase inhibitors
Beta-lactamase inhibitor combo spectrum of activity against gram-positives
MSSA (not a lot of clinical studies done)
Beta-lactamase inhibitor combo spectrum of activity against gram-negatives
-H. influenzae
-E. Coli
-Proteus spp.
-Klebsiella spp.
-Neisseria gonorrhoeae
-Moraxella catarrhalis
Beta-lactamase inhibitor combo spectrum of activity against anaerobes
Bacterioides spp. (great activity against BDA)*
What are penicillins dependent on to kill bacteria?
-Time-dependent bacterial killing
-Time above MIC (Time>MIC)
What is the goal of dosing in penicillins?
Administer agents to maintain serum concentrations > MIC of infecting bacteria for 50% of dosing interval
What synergy is used clinically to treat Viridans strep?
Penicillin or ampicillin plus gentamicin
What synergy is used clinically to treat enterococcus spp.?
Ampicillin plus gentamicin or streptomycin
What synergy is used clinically to treat staphylococcus spp.)
Nafcillin plus gentamicin
What synergy is used clinically to treat gram negative bacteria?
Ticarcillin or piperacillin plus gentamicin, tobramycin or amikacin
When should you use oral vs IV penicillins?
Oral penicillins should be used for mild to moderate disease and IV should be used for moderate to severe disease
Do penicillins penetrate into the CNS?
Adequate concentrations of penicillins (but NOT beta-lactamase inhibitors) are achieved ONLY in the presence of inflamed meninges with high-dose parenteral administration
What is the elimination half life of penicillins?
Short
How are penicillins eliminated?
Most are eliminated through the liver
Which penicillins do not need their doses to be adjusted due to renal insufficiency?
-Nafcillin
-Oxacillin
Which penicillins contain sodium in their preparations?
-Sodium penicillin G
-Nafcillin
-Ticarcillin
-Piperacillin
Sodium content of sodium penicillin G
2 mEq per 1 million units
Sodium content of sodium nafcillin
2.9 mEq per gram
Sodium content of sodium ticarcillin
5.2 mEq per gram
Sodium content of sodium piperacillin
1.85 mEq per gram
Clinical use of natural penicillins
Syphilis
Clinical use of penicillinase-resistant penicillins
MSSA
Clinical use of aminopenicillins
-Enterococcal infections
-Listeria monocytogenes
Clinical use of carboxypenicillins and ureidopenicillins
-Gram-negative aerobic bacteria
-Hospital-acquired infections
-Infections due to pseudomonas aeruginosa (piperacillin)
Clinical use of Augmentin
-Sinusitis
-Otitis media
Clinical use of Unasyn, Zosyn
-Polymicrobial infections
-Empiric therapy for febrile neutropenia
-Hospital-acquired infections (Zosyn)
Adverse effects of penicillins
-Hypersensitivity
-Neurologic effects: seizures
-Hematologic: Neutropenia, thrombocytopenia
-GI effects
-Interstitial nephritis: abrupt increase in serum creatinine
-Phlebitis
-Hypokalemia
-Na overload
Is there cross-reactivity among penicillins?
Yes and some other beta-lactams
What can cause neurologic adverse effects in patients taking penicillins?
Patients receiving high IV doses in the presence of renal insufficiency
How can you reverse hematologic adverse effects in patients taking penicillins?
Discontinue the medication
Which medications are most likely to cause interstitial nephritis?
Methicillin or nafcillin
